Coating for medical device having increased surface area

ABSTRACT

Described herein are implantable medical devices for delivering a therapeutic agent to the body tissue of a patient, and methods for making such medical devices. In particular, the implantable medical devices, such as intravascular stents, have a coating which includes at least one coating composition and has an exposed abluminal surface and an exposed luminal surface or exposed side surface.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of, and claims benefit under 35 USC120 to, international application PCT/US2008/008900, filed Jul. 22,2008, which claims benefit of U.S. Ser. No. 60/953,736, filed Aug. 3,2007. International application PCT/US2008/008900 is hereby incorporatedby reference in its entirety.

INTRODUCTION

Described herein are implantable medical devices for delivering atherapeutic, agent to the body tissue of a patient, and methods formaking such medical devices. In particular, certain embodiments aredirected to implantable medical devices, such as intravascular stents,having a coating with increased surface area, wherein the coatingincludes at least one coating composition that has an exposed abluminalsurface and an exposed luminal surface or an exposed side surface.

BACKGROUND

Medical devices comprising a therapeutic agent have been successful intreating the body tissue of a patient. For example, intravascular stentsthat have a coating containing, a therapeutic agent for preventingrestenosis have been successful in reducing incidents of restenosis. Incertain instances, in order to improve the reduction of restenosis, itmay be desirable to increase the amount of the therapeutic agent that isdelivered from the coating to the body tissue.

One way of increasing the amount of therapeutic agent that is deliveredto the body tissue is to increase the amount of the therapeutic agentthat is loaded into the coating. However, there are difficultiesassociated with coatings that contain large amounts of a therapeuticagent, such as controlling the release of the therapeutic agent.Particularly, larger amounts of therapeutic agents in the coating can bereleased too rapidly from the coating, thereby creating a “burst” effectinstead of a desired sustained release of the therapeutic agent.

Another way of increasing the amount of therapeutic agent that isincluded in a medical device coating and delivered to the body tissue isto increase the surface area of the coating that is exposed to thetissue. In general, when a coating composition is disposed on thesurface of a medical device, such as a stent, the exposed surface areaof the coating is generally equivalent to the surface area of themedical device upon which the coating is disposed. Thus, the surfacearea of the medical device surface limits the exposed surface area ofthe coating.

One way to increase the exposed surface area of the coating is to removematerial from the surface of the medical device to increase the surfacearea upon which a coating can be disposed. However, removing materialfrom the medical device can adversely impact the structural integrity ofthe medical device. For example, if holes are created in the struts of astent, the structural integrity of the stent struts can be compromisedcausing the struts to become weak. Weak struts could result in the stentfailing to expand properly or, once implanted, collapsing, potentiallycausing re-occlusion of a body lumen.

Accordingly, there is a need for a medical device having a coating withan increased exposed surface area for delivering a therapeutic agent tobody tissue. Furthermore, there is a need for methods of making suchmedical device coatings having increased exposed surface area that donot adversely affect the structural integrity of the medical device

SUMMARY

These and other objectives are addressed by the coatings and medicaldevices described herein. Described herein are medical devices, such asintravascular stents, that comprise a coating having an increasedexposed surface area for delivering a therapeutic agent to a patient.The increased exposed surface area of the coating allows a greateramount of a therapeutic agent to be delivered from the coating in acontrolled release manner, thereby avoiding any undesirable early orrapid release of the therapeutic agent. Moreover, the coatings describedherein are capable of accomplishing the above objectives withoutcompromising the structural integrity of the medical device.

Certain embodiments include an implantable stent having a stent sidewallstructure having an abluminal surface and a luminal surface opposite theabluminal surface and a coating comprising a coating compositiondisposed on at least a portion of the abluminal surface. The coating hasan exposed abluminal surface and an exposed luminal surface or anexposed side surface. An exposed surface is a surface that is notcovered by another material.

Some embodiments include an implantable intravascular stent having astent sidewall structure comprising a plurality of struts and aplurality of openings in the stent sidewall structure. At least onestrut has an abluminal surface and a luminal surface opposite theabluminal surface. A coating comprising a coating composition isdisposed directly on at least a portion of the abluminal surface of astrut such that the coating has an exposed abluminal surface and anexposed luminal surface or an exposed side surface. The coatingcomposition comprises a biostable polymer and an anti-restenosis agent.

Other embodiments include an implantable stent having a stent sidewallstructure having an abluminal surface and a luminal surface opposite theabluminal surface and a coating disposed on at least a portion of theabluminal surface. The coating includes a first coating compositiondisposed on at least a portion of the abluminal surface and a secondcoating composition disposed on the first coating composition. Thecoating has an exposed abluminal surface and an exposed luminal surfaceor an exposed side surface.

Still other embodiments include an implantable intravascular stenthaving a stent sidewall structure comprising a plurality of struts and aplurality of openings in the stent sidewall structure. At least onestrut has an abluminal surface and a luminal surface opposite theabluminal surface. A coating is disposed on at least a portion of theabluminal surface of a strut. The coating includes a first coatingcomposition disposed directly on at least a portion of the abluminalsurface of the strut, wherein the first coating composition comprises afirst biostable polymer, and a second coating composition disposeddirectly on the first coating composition. The second coatingcomposition includes a second biostable polymer and an anti-restenosisagent. The coating has an exposed abluminal surface and an exposedluminal surface or an exposed side surface.

Other embodiments described herein include an implantable stent having astent sidewall structure having an abluminal surface and a luminalsurface opposite the abluminal surface and a coating disposed on atleast a portion of the abluminal surface. The coating includes a firstcoating composition disposed on at least a portion of the abluminalsurface, a second coating composition disposed on the first coatingcomposition and a third coating composition disposed on the secondcoating composition. The coating has an exposed abluminal surface and anexposed luminal surface or an exposed side surface.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an example of a stent that is suitable for use in theembodiments described herein.

FIGS. 2A-2F show cross-sectional views of embodiments where a portion ofa stent strut has a coating composition disposed thereon.

FIGS. 3A-3E show cross-sectional views of embodiments where a portion ofa stent strut has two coating compositions disposed thereon.

FIG. 4A-4C show cross-sectional views of embodiments where a portion ofa stent strut has three coating compositions disposed thereon.

FIG. 5 shows a perspective view of a portion of a stent strut having acoating that extends along a portion of the strut.

FIG. 6 shows a perspective view of another stent strut having a coatingdisposed on portions of the surface of the stent strut.

FIG. 7 shows a perspective view of a stent having a coating that forms amirror-image of the portion of abluminal surface of the stent upon whichthe coating is disposed.

FIGS. 8A-8H show cross-sectional views of additional embodiments where aportion of a stent strut has a coating composition disposed thereon.

FIG. 9A-9B show a method for making a coated medical device inaccordance with the methods described herein.

FIG. 10A-10C show another method for making a coated medical device inaccordance with the methods described herein.

FIG. 11A-11D show yet another method for making a coated medical devicein accordance with the methods described herein.

FIG. 12A-12D show still another method for making a coated medicaldevice in accordance with the methods described herein.

FIG. 13A-13E show another method for making a coated medical device inaccordance with the methods described herein.

FIG. 14A-14C show yet another method for making a coated medical devicein accordance with the methods described herein.

DETAILED DESCRIPTION

The coatings of the embodiments described herein can be used inconnection with any medical device that has a surface. FIG. 1 shows anexample of a medical device that is suitable for use in the embodimentsdescribed herein. This figure shows an implantable intravascular stent10 comprising a sidewall 20 which has a first sidewall surface 22 and anopposing second sidewall surface, which is not shown in FIG. 1. Thefirst sidewall surface 22 can be an outer or abluminal sidewall surface,which faces the body lumen wall when the stent is implanted, or an inneror luminal sidewall surface, which faces away from the body lumen walland towards the center of the lumen. Stent 10 also has a plurality ofstruts 30 and at least one opening 40 in the sidewall 20. Generally, theopening 40 is disposed between adjacent struts 30. Suitable stentsidewall structures have a plurality of struts and openings and whereinat least one strut comprises an abluminal surface, which forms part ofthe abluminal surface of the stent upon which the coating composition isdisposed, and the strut comprises a luminal surface opposite theabluminal surface of the strut, which forms part of the luminal surfaceof the stent. In a stent having an opening in the stent sidewallstructure, in certain embodiments, it is preferable that the coatingapplied to the stent conforms to the surface of the stent so that theopenings in the sidewall stent structure are preserved, e.g. theopenings are not entirely or partially occluded with coating material.

FIG. 2 A shows a cross-sectional view of an embodiment where a portionof a stent strut 50 has a coating 60 comprising a coating composition 62disposed thereon. The stent strut 50 has an abluminal surface 52 and aluminal surface 54. In this embodiment, a coating 60 is disposed on theabluminal surface 52 of stent strut 50. The coating includes a coatingcomposition 62 comprising a coating material 64, such as a polymer,metal, metal oxide, ceramic oxide, inert carbon or combination thereof,and a therapeutic agent 66. Also, the coating material 64 can be thesame or different from the material that forms the strut 50. The coatingcomposition 62 has an exposed abluminal surface 68, which faces theluminal wall, an exposed luminal surface 69, which faces the center ofthe lumen and exposed side surfaces 65.

Unlike coatings that only have an exposed abluminal surface, e.g. thesurface of the coating that faces the body lumen, from which thetherapeutic agent can be released, the coatings described herein alsoinclude an exposed luminal surface 69, e.g. the surface of the coatingthat faces the center of the lumen, from which the therapeutic agent 66can be released, or exposed side surfaces 65, e.g. surfaces that areperpendicular to or at an angle with an abluminal or luminal surface.The embodiment of the coating shown in FIG. 2 A has an exposed abluminalsurface 68, an exposed luminal surface 69 and two exposed side surfaces65. Therefore, in the embodiment shown in FIG. 2A, a therapeutic agentcan be released from surfaces 68 and 69, as well as, surfaces 65. Theincreased surface area from which the therapeutic agent can be releasedallows more of the therapeutic agent in the coating to be released andless of the therapeutic agent to remain unused in the coating.

As shown in FIG. 2 A, the luminal surface 54 of the strut, which is thesurface that faces the center of the body lumen and faces away from thebody lumen wall, is substantially free of the coating 60. As used hereinthe phrase, “substantially free of the coating” means that the coatingis not intentionally disposed on the surface. In alternativeembodiments, a coating can be disposed on the luminal surface as well asthe abluminal surface. The coating disposed on the luminal surface canbe the same or different from the coating disposed on the abluminalsurface. For example, the coating disposed on the abluminal surface caninclude a coating composition comprising a therapeutic agent that can beexposed or introduced to a blood vessel wall. The coating disposed onthe luminal surface can include a coating composition comprising atherapeutic agent or surface that can be exposed or introduced to thebloodstream. In another embodiment, the coating disposed on the luminalsurface can include a coating composition without a therapeutic agent.In other embodiments, a coating can be disposed on the luminal surfacewhile the abluminal surface is substantially free of any coating.

FIG. 2B shows another embodiment of a coating 60 comprising a coatingcomposition 62 having an exposed abluminal surface 68, an exposedluminal surface 69 and two exposed side surfaces 65. Coating 60 alsoincludes a coating composition 64 and a therapeutic agent 66. Unlike theembodiment shown in FIG. 2A, in this embodiment the strut 50 comprises aportion 58 that extends past its abluminal surface 52. The coatingcomposition 62 is disposed on the extended portion 58.

The embodiments shown in FIGS. 2C and 2D are respectively similar tothose shown in FIGS. 2A and 2B. However, in the coatings 60 shown inFIGS. 2C and 2D, the therapeutic agent 66 is not dispersed throughoutthe coating composition 62. Instead, the therapeutic agent 66 isdisposed at or near the exposed abluminal surface 68, exposed luminalsurface 69 and exposed side surfaces 65 of the coating composition 62.

In the embodiments shown in FIGS. 2A-2D, the coating composition 62 isdisposed directly on, i.e. in physical contact with a strut surface.FIGS. 2E and 2F show two embodiments where the coating composition 62 isnot disposed directly on the surface 52 of the strut 50. Instead, anintervening material 56, such as an adhesive or other material thatenhances the adhesion of the coating composition to the strut surface,is disposed between the coating composition 62 and the strut surface 52.

FIGS. 3A-3E show cross-sectional views of embodiments where coatingscomprising first and second coating compositions are disposed on a stentstrut surface. In FIG. 3 A, the coating 160 comprises a first coatingcomposition 170 disposed on at least a portion of the abluminal surface152 of a stent strut 150. A second coating composition 162 is disposedon the first coating composition 170. The second coating composition 162has an exposed abluminal surface 168, an exposed luminal surface 169 andexposed side surfaces 165. The first coating composition 170 comprises afirst coating material 172, such as a polymer, metal, metal oxide,ceramic oxide, inert carbon or combination thereof. The second coatingcomposition 162 comprises a second coating material 164, such as apolymer, metal, metal oxide, ceramic oxide, inert carbon or combinationthereof. The first coating composition 170 can be the same or differentas the second coating composition 162. Moreover, the first or secondcoating materials 172, 164 can be the same or different from thematerial that forms the strut 150. As shown in FIG. 3A, the secondcoating composition 162 also includes a therapeutic agent 166. Incertain embodiments, the first coating composition 170 can also includea therapeutic agent that is the same as or different from thetherapeutic agent 166 of the second coating composition 162.

In certain embodiments, the first coating composition has a firstexposed abluminal surface area when disposed on the abluminal surface,prior to the deposition of the second coating composition, and thesecond coating composition comprises a second exposed abluminal surfacearea when disposed on the first coating composition, wherein the secondexposed abluminal surface area is greater than the first exposedabluminal surface area.

FIG. 3B shows another embodiment that is similar to that shown in FIG.2B except that the coating 160 comprises a first and second coatingcomposition 170, 162. In particular, in FIG. 3 B, the coating 160comprises a first coating composition 170 that is disposed on a portion158 of the stent strut 150 that extends past its abluminal surface 152.A second coating composition 162 is disposed on the first coatingcomposition 170 and the second coating composition 162 has an exposedabluminal 168, an exposed luminal surface 169 and exposed side surfaces165.

The embodiment shown in FIG. 3C is similar to that shown in FIG. 3A.However, in the coating 160 shown in FIG. 3C, the therapeutic agent 166is not dispersed throughout the second coating composition 162. Instead,the therapeutic agent 166 is disposed at or near the exposed abluminal168, exposed luminal 169 and exposed side surfaces 165 of the secondcoating composition 162.

FIG. 3D shows an embodiment with a coating 160 comprising a first andsecond coating composition 170, 162 where the first coating composition170 has an abluminal surface 174 and luminal surface 176 as well as twoside surfaces 178. The second coating composition 162 is disposed on theabluminal surface 174, luminal surface 176 and two side surfaces 178 ofthe first coating composition 170. The second coating composition has anexposed abluminal surface 168, an exposed luminal surface 169 andexposed side surfaces 165.

FIGS. 3A-3D show the first coating composition 170 disposed directly onthe abluminal 152 surface of the stent strut 150 and the second coatingcomposition 162 disposed directly on the first coating composition 170;however, in other embodiments, an intervening material can be disposedbetween the first coating composition 162 and the abluminal surface 152of the strut 150, such that the first coating composition would not bedisposed directly on the abluminal surface of the stent. Alternatively,an intervening material can be disposed between the first coatingcomposition 162 and the second coating composition 170, such that thefirst coating composition would not be disposed directly on the secondcoating composition. FIG. 3E shows a coating 160 comprising a first andsecond coating composition 170, 162 with an intervening material 156,such as an adhesive agent, shown in FIGS. 2E and 2F, disposed betweenthe two coating compositions.

The coating disposed on the abluminal surface of a medical device canalso include a first coating composition disposed on at least a portionof the surface of a medical device, a second coating compositiondisposed on the first coating composition and a third coatingcomposition containing a therapeutic agent disposed on the exposedsurfaces of the second coating composition, wherein the third coatingcomposition has an exposed abluminal surface and an exposed luminalsurface, as shown in FIGS. 4A-4C.

FIG. 4A shows a stent strut 250 having an abluminal surface 252, aluminal surface 254, and a coating 260. The coating 260 comprises afirst coating composition 280 disposed on at least a portion of theabluminal surface 252 of a stent strut 250. A second coating composition270 is disposed on the first coating composition 280 and a third coatingcomposition 262 is disposed on the second coating composition 270. Thethird coating composition 262 has an exposed abluminal surface 268, anexposed luminal surface 269 and exposed side surfaces 265. The firstcoating composition 280 includes a first coating material 282, such as apolymer, metal, metal oxide, ceramic oxide, inert carbon or combinationthereof. The second coating composition 270 comprises a second coatingmaterial 272, such as a polymer, metal, metal oxide, ceramic oxide,inert carbon or combination thereof. The third coating composition 262comprises a third coating material 264, such as a polymer, metal, metaloxide, ceramic oxide, inert carbon or combination thereof. The first,second or third coating compositions 280, 270, 262 can include the sameor different materials. Moreover, the first, second or third coatingmaterials 282, 272, 264 can be the same or different from the materialthat forms the strut 250. As shown in FIG. 4A, the third coatingcomposition 262 also includes a therapeutic agent 266. In certainembodiments, the first or second coating composition 280 and 270 canalso include a therapeutic agent that is the same or different from thetherapeutic agent 266 of the third coating composition 262.

FIG. 4B shows a coating that includes three coating compositions. Thecoating 260 includes a first coating composition 280 directly disposedon a portion 258 of the stent strut 250 that extends past its abluminalsurface 252. A second coating composition 270 is disposed on the firstcoating composition 280 and a third coating composition 262 is disposedon the second coating composition 270. The third coating composition 262has an exposed abluminal 268, an exposed luminal surface 269 and exposedside surfaces 265, as well as a therapeutic agent 266 disposed therein.

FIGS. 4A and 4B show the third coating composition disposed directly onthe second coating composition and the second coating compositiondisposed directly on the first coating composition, however, the thirdand second coating compositions do not have to be disposed directly onthe second and first coating compositions. FIG. 4C shows a coating 260comprising a first, second and third coating composition 280, 270, 262with an intervening material 256 disposed between the first and secondcoating compositions 280 and 270. In other embodiments, an interveningmaterial can be disposed between the first coating composition 280 andthe abluminal surface 252 of the strut 250.

Compared to the embodiments shown in FIGS. 2A-2F, 3A-3E and 4A-4C whichare cross-sectional views, FIG. 5 shows a perspective view of a coatingsimilar to that of FIG. 2A in which the coating 60 extends along thelength of the strut 50. The strut 50 has an abluminal surface 52 and aluminal surface 54. Coating 60 is disposed on the abluminal surface 52of the strut. Coatings such as those shown in the above-describedfigures can also be disposed on a strut in this configuration. Thecoating 60 comprises a coating composition 62 that has an exposedabluminal 68, an exposed luminal surface 69, and exposed side surfaces65, as well as a therapeutic agent 66.

FIG. 6 shows a perspective view of another embodiment in which a coating360 includes a coating composition 362 disposed on certain portions ofthe abluminal surface 352 of the stent strut 350. The coating 360 has anexposed abluminal 368, an exposed luminal surface 369 and exposed sidesurfaces 365. The coating composition 362 includes a coating material364 and a therapeutic agent 366. Although the coating composition,disposed on the portions of the stent struts is the same in this figuresuch coating compositions can be different. Also, additional coatingcompositions can be disposed on the luminal surface of the stent strut.

In some embodiments, the coating disposed on a portion of the stentsurface can be a mirror-image of the portion of the stent surface. Forexample, FIG. 7 shows a perspective view of a portion of a stent 410 inwhich a coating 460 is disposed on a portion of the abluminal surface452 of the stent. The coating 460 includes a coating composition 462that includes a coating material 464 and a therapeutic agent 466. Thecoating composition 462 has an exposed abluminal surface 468, an exposedluminal surface 469 and an exposed side surface 467. The abluminal andluminal surface 468 and 469 of the coating composition are mirror-imagesof the portion of the abluminal surface 452 upon which the coating 460is disposed. The coating can be prefabricated in the form of amirror-image of the surface before being disposed on the surface.

In certain embodiments, the coatings can have a cross-section in theshape of a “T” as shown in FIG. 2 or an inverted “T” as shown in FIG.8A. FIG. 8A shows a coating 500 that has exposed abluminal surfaces 502and exposed side surfaces 504. In other embodiments, the cross-sectionof the coating can be in the shape of a modified “T”. For instance, asshown in FIG. 8B, the cross-section of the coating 510 can have anexposed abluminal surface 512, exposed luminal surface 513 and exposedside surfaces 514 with rounded edges 516 and curved surfaces 517. In theembodiment shown in FIG. 8C, the coating 520 has a cross-section in theshape of another modified “T” in which the exposed abluminal surface522, exposed luminal surface 524 and exposed side surfaces 526 of the“T” have ridges 528. The ridges further increase the exposed surfacearea of the coating.

In still other embodiments, the cross-section of the coating can be inthe form of other shapes. Other suitable shapes are shown in FIG. 8Dthrough FIG. 8H. FIG. 8D shows the cross-section of a coating 530 in theshape of an “I” with an exposed abluminal surface 532, an exposedluminal surface 534 and exposed side surfaces 536. FIG. 8E shows thecross-section of a coating 540 having a “V” shape. The coating hasexposed abluminal surfaces 542 and exposed luminal surface 544. FIG. 8Fshows the cross-section of a coating 550, which is shaped like an “E”,rotated 90°, with exposed abluminal surfaces 552 and exposed sidesurfaces 554. FIG. 8G shows the cross-section of a coating 560, which isshaped like a “U”, with exposed abluminal surfaces 562 and exposed sidesurfaces 564. FIG. 8H shows the triangular cross-section of a coating570 with an exposed abluminal surface 572 and exposed luminal surfaces564.

The coatings may be of any thickness. In some embodiments, the coatingcan have a thickness of about 5 microns to about 40 microns. Preferablythe coatings have a thickness of about 5 microns to about 15 microns. Insome instances, a relatively thicker coating may be preferred toincorporate greater amounts of a therapeutic agent. Coatings of theembodiments described herein may include multiple layers of coatingcompositions. For example, coatings can include multiple layers ofdifferent coating compositions or multiple layers of the same coatingcomposition.

The coating compositions described herein may also include a pluralityof pores. The pores can extend from the surface of a coating compositionto the surface of another coating composition or the surface of themedical device. The pores can be any shape including but not limited to,channels, void pathways or microscopic conduits, spheres or hemispheres.Additionally, the pores can have any size or range of sizes. In someinstances, the pores can be micropores or nanopores. The pores can alsobe distributed throughout the coating composition or located in specificareas of the coating composition, such as near the exposed surfaces ofthe coating compositions. In certain embodiments the pores are locatednear the exposed abluminal and the exposed luminal surface of a coatingcomposition. Also, pores can be distributed randomly or in a pattern. Incertain embodiments, wherein the coating composition also includes atleast one therapeutic agent, the therapeutic agent can be disposed in atleast some or all of the pores.

A. Medical Devices

Medical devices which are suitable for the embodiments described hereininclude any stent for medical purposes, which are known to the skilledartisan. Suitable stents include, for example, vascular stents such asself-expanding stents and balloon expandable stents. Examples ofself-expanding stents are illustrated in U.S. Pat. Nos. 4,655,771 and4,954,126 issued to Wallsten and U.S. Pat. No. 5,061,275 issued toWallsten et al. Examples of appropriate balloon-expandable stents areshown in U.S. Pat. No. 5,449,373 issued to Pinchasik et al. In preferredembodiments, a suitable stent is an Express stent. More preferably, theExpress stent is an Express™ stent or an Express2™ stent (BostonScientific, Inc. Natick, Mass.).

The framework of the suitable stents may be formed through variousmethods as known in the art. The framework may be welded, molded, lasercut, electro-formed, or consist of filaments or fibers which are woundor braided together in order to form a continuous structure.

Medical devices that are suitable for the embodiments described hereinmay be fabricated from metallic, ceramic, polymeric or compositematerials or a combination thereof. In some instances, the medicaldevice can be made of a non-polymeric material. Preferably, thematerials are biocompatible. Metallic material is more preferable.Suitable metallic materials include metals and alloys based on titanium(such as nitinol, nickel titanium alloys, thermo-memory alloymaterials); stainless steel; tantalum, nickel-chrome; or certain cobaltalloys including cobalt-chromium-nickel alloys such as Elgiloy® andPhynox®; PERSS (Platinum EnRiched Stainless Steel) and Niobium. Metallicmaterials also include clad composite filaments, such as those disclosedin WO 94/16646.

Suitable ceramic materials include, but are not limited to, oxides,carbides, or nitrides of the transition elements such as titanium,hathium, iridium, chromium, aluminum, and zirconium. Silicon basedmaterials, such as silica, may also be used.

Suitable polymers for forming the medical devices may be biostable.Also, the polymer may be biodegradable. Suitable polymers include, butare not limited to, styrene isobutylene styrene, polyetheroxides,polyvinyl alcohol, polyglycolic acid, polylactic acid, polyamides,poly-2-hydroxy-butyrate, polycaprolactone, poly(lactic-co-glycolic)acid,and Teflon.

Polymers that may be used for forming the medical device in theembodiments described herein include, without limitation,isobutylene-based polymers, polystyrene-based polymers, polyacrylates,and polyacrylate derivatives, vinyl acetate-based polymers and itscopolymers, polyurethane and its copolymers, silicone and itscopolymers, ethylene vinyl-acetate, polyethylene terephtalate,thermoplastic elastomers, polyvinyl chloride, polyolefins, cellulosics,polyamides, polyesters, polysulfones, polytetrafluorethylenes,polycarbonates, acrylonitrile butadiene styrene copolymers, acrylics,polylactic acid-polyethylene oxide copolymers, cellulose, collagens, andchitins.

Other polymers that are useful as materials for medical devices includewithout limitation dacron polyester, polymethylmethacrylate,polypropylene, polyalkylene oxalates, polysiloxanes, nylons,poly(dimethyl siloxane), polycyanoacrylates, polyphosphazenes,poly(amino acids), ethylene glycol I dimethacrylate, poly(methylmethacrylate), poly(2-hydroxyethyl methacrylate),polytetrafluoroethylene poly(HEMA), polyhydroxyalkanoates,polytetrafluorethylene, polycarbonate, poly(γ-hydroxybutyrate),polydioxanone, poly(γ-ethyl glutamate), polyiminocarbonates, poly(orthoester), polyanhydrides, alginate, dextran, cotton, polyurethane, orderivatized versions thereof, i.e., polymers which have been modified toinclude, for example, attachment sites or cross-linking groups, e.g.,RGD, in which the polymers retain their structural integrity whileallowing for attachment of cells and molecules, such as proteins,nucleic acids, and the like.

B. Coating Materials and Intervening Materials

The coating compositions of described herein can comprise of any coatingmaterial such as, but not limited to, polymers, metal oxides, ceramicoxides, metals, inert carbon or combinations thereof. Additionally, thecoating compositions can be radiopaque and/or have MRI compatibility. Asdiscussed above the coating compositions described herein can becomprised of the same material or materials or different material ormaterials.

Polymers

Polymers useful for use in the coating compositions described hereinshould be ones that are biocompatible, particularly during insertion orimplantation of the device into the body and avoids irritation to bodytissue. Suitable polymers can be biostable or, alternatively,biodegradable. Examples of such polymers include, but not limited to,polyurethanes, polyisobutylene and its copolymers, silicones, andpolyesters. Other suitable polymers include polyolefins,polyisobutylene, ethylene-alphaolefin copolymers, acrylic polymers andcopolymers, vinyl halide polymers and copolymers such as polyvinylchloride, polyvinyl ethers such as polyvinyl methyl ether,polyvinylidene halides such as polyvinylidene fluoride andpolyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polyvinylaromatics such as polystyrene, polyvinyl esters such as polyvinylacetate; copolymers of vinyl monomers, copolymers of vinyl monomers andolefins such as ethylene-methyl methacrylate copolymers,acrylonitrile-styrene copolymers, ABS resins, ethylene-vinyl acetatecopolymers, polyamides such as Nylon 66 and polycaprolactone, alkydresins, polycarbonates, polyoxyethylenes, polyimides, polyethers, epoxyresins, polyurethanes, rayon-triacetate, cellulose, cellulose acetate,cellulose butyrate, cellulose acetate butyrate, cellophane, cellulosenitrate, cellulose propionate, cellulose ethers, carboxymethylcellulose, collagens, chitins, polylactic acid, polyglycolic acid, andpolylactic acid-polyethylene oxide copolymers.

In certain embodiments, hydrophobic polymers can be used. Examples ofsuitable hydrophobic polymers or monomers include, but not limited to,polyolefins, such as polyethylene, polypropylene, poly(1-butene),poly(2-butene), poly(1-pentene), poly(2-pentene),poly(3-methyl-1-pentene), poly(4-methyl-1-pentene), poly(isoprene),poly(4-methyl-1-pentene), ethylene-propylene copolymers,ethylene-propylene-hexadiene copolymers, ethylene-vinyl acetatecopolymers, blends of two or more polyolefins and random and blockcopolymers prepared from two or more different unsaturated monomers;styrene polymers, such as poly(styrene), styrene-isobutylene copolymers,poly(2-methylstyrene), styrene-acrylonitrile copolymers having less thanabout 20 mole-percent acrylonitrile, andstyrene-2,2,3,3,-tetrafluoropropyl methacrylate copolymers; halogenatedhydrocarbon polymers, such as poly(chlorotrifluoroethylene),chlorotrifluoroethylene-tetrafluoroethylene copolymers,poly(hexafluoropropylene), poly(tetrafluoroethylene),tetrafluoroethylene, tetrafluoroethylene-ethylene copolymers,poly(trifluoroethylene), poly(vinyl fluoride), and poly(vinylidenefluoride); vinyl polymers, such as poly(vinyl butyrate), poly(vinyldecanoate), poly(vinyl dodecanoate), poly(vinyl hexadecanoate),poly(vinyl hexanoate), poly(vinyl propionate), poly(vinyl octanoate),poly(heptafluoroisopropoxyethylene),poly(heptafluoroisopropoxypropylene), and poly(methacrylonitrile);acrylic polymers, such as poly(n-butyl acetate), poly(ethyl acrylate),poly(1-chlorodifluoromethyl)tetrafluoroethyl acrylate, polydi(chlorofluoromethyl)fluoromethyl acrylate,poly(1,1-dihydroheptafluorobutyl acrylate),poly(1,1-dihydropentafluoroisopropyl acrylate),poly(1,1-dihydropentadecafluorooctyl acrylate),poly(heptafluoroisopropyl acrylate), poly5-(heptafluoroisopropoxy)pentyl acrylate, poly11-(heptafluoroisopropoxy)undecyl acrylate, poly2-(heptafluoropropoxy)ethyl acrylate, and poly(nonafluoroisobutylacrylate); methacrylic polymers, such as poly(benzyl methacrylate),poly(n-butyl methacrylate), poly(isobutyl methacrylate), poly(t-butylmethacrylate), poly(t-butylaminoethyl methacrylate), poly(dodecylmethacrylate), poly(ethyl methacrylate), poly(2-ethylhexylmethacrylate), poly(n-hexyl methacrylate), poly(phenyl methacrylate),poly(n-propyl methacrylate), poly(octadecyl methacrylate),poly(1,1-dihydropentadecafluorooctyl methacrylate),poly(heptafluoroisopropyl methacrylate), poly(heptadecafluorooctylmethacrylate), poly(1-hydrotetrafluoroethyl methacrylate),poly(1,1-dihydrotetrafluoropropyl methacrylate),poly(1-hydrohexafluoroisopropyl methacrylate), andpoly(t-nonafluorobutyl methacrylate); polyesters, such a poly(ethyleneterephthalate) and poly(butylene terephthalate); condensation typepolymers such as and polyurethanes and siloxane-urethane copolymers;polyorganosiloxanes, i.e., polymers characterized by repeating siloxanegroups, represented by Ra SiO 4-a/2, where R is a monovalent substitutedor unsubstituted hydrocarbon radical and the value of a is 1 or 2; andnaturally occurring hydrophobic polymers such as rubber.

In alternative embodiments, hydrophilic polymers can be used. Examplesof suitable hydrophilic polymers or monomers include, but not limitedto; (meth)acrylic acid, or alkaline metal or ammonium salts thereof;(meth)acrylamide; methylenebisacrylamide; (meth)acrylonitrile;polylactic acid; polyglycolic acid; polylactic-glycolic acid; thosepolymers to which unsaturated dibasic, such as maleic acid and fumaricacid or half esters of these unsaturated dibasic acids, or alkalinemetal or ammonium salts of these dibasic adds or half esters, is added;those polymers to which unsaturated sulfonic, such as2-acrylamido-2-methylpropanesulfonic, 2-(meth)acryloylethanesulfonicacid, or alkaline metal or ammonium salts thereof, is added; and2-hydroxyethyl(meth)acrylate and 2-hydroxypropyl(meth)acrylate.

Polyvinyl alcohol is also an example of hydrophilic polymer. Polyvinylalcohol may contain a plurality of hydrophilic groups such as hydroxyl,amido, carboxyl, amino, ammonium or sulfonyl (—SO3). Hydrophilicpolymers also include, but are not limited to, starch, polysaccharidesand related cellulosic polymers; polyalkylene glycols and oxides such asthe polyethylene oxides; polymerized ethylenically unsaturatedcarboxylic acids such as acrylic, mathacrylic and maleic acids andpartial esters derived from these acids and polyhydric alcohols such asthe alkylene glycols; homopolymers and copolymers derived fromacrylamide; and homopolymers and copolymers of vinylpyrrolidone.

Additional suitable polymers include, but are not limited to,thermoplastic elastomers in general, polyolefins, polyisobutylene,ethylene-alphaolefin copolymers, acrylic polymers and copolymers, vinylhalide polymers and copolymers such as polyvinyl chloride, polyvinylethers such as polyvinyl methyl ether, polyvinylidene halides such aspolyvinylidene fluoride and polyvinylidene chloride, polyacrylonitrile,polyvinyl ketones, polyvinyl aromatics such as polystyrene, polyvinylesters such as polyvinyl acetate, copolymers of vinyl monomers,copolymers of vinyl monomers and olefins such as ethylene-methylmethacrylate copolymers, acrylonitrile-styrene copolymers, ABS(acrylonitrile-butadiene-styrene) resins, ethylene-vinyl acetatecopolymers, polyamides such as Nylon 66 and polycaprolactone, alkydresins, polycarbonates, polyoxymethylenes, polyimides, polyethers,polyether block amides, epoxy resins, rayon-triacetate, cellulose,cellulose acetate, cellulose butyrate, cellulose acetate butyrate,cellophane, cellulose nitrate, cellulose propionate, cellulose ethers,carboxymethyl cellulose, collagens, chitins, polylactic acid,polyglycolic acid, polylactic acid-polyethylene oxide copolymers, EPDM(ethylene-propylene-diene) rubbers, fluoropolymers, fluorosilicones,polyethylene glycol, polysaccharides, phospholipids, and combinations ofthe foregoing. In certain embodiments preferred polymers include, butare not limited to, polylactic acid; polyglycolic acid;polylactic-glycolic acid, styrene-isobutylene-styrene copolymers orcombinations thereof.

Metal or Ceramic Oxides

In certain embodiments, the coating compositions can include a metaloxide and/or a ceramic oxide. Examples of metal oxides or ceramic oxidesinclude without limitation, platinum oxides, tantalum oxides, titaniumoxides, tantalum oxides, zinc oxides, iron oxides, magnesium oxides,aluminum oxides, iridium oxides, niobium oxides, zirconium oxides,tungsten oxides, rhodium oxides, ruthenium oxides, silicone oxides suchas, silicon dioxide; or combinations thereof. Preferred metal oxides andceramic oxides include iridium oxide, zirconium oxide, titanium oxide,zinc oxide or combinations thereof.

Metals

In certain embodiments, the coating compositions can include a metal.Suitable metals include alkali metals, alkaline earth metals, transitionmetals, metal alloys and metalloids. Examples of metals include withoutlimitation, titanium, scandium, stainless steel, tantalum, nickel,silicon, chrome, cobalt, chromium, manganese, iron, platinum, iridium,niobium, vanadium, zirconium, tungsten, rhodium, ruthenium, gold,copper, zinc, yttrium, molybdenum, technetium, palladium, cadmium,hafnium, rhenium and combinations thereof. In certain embodimentspreferred metals include without limitation, platinum, tantalum,magnesium or combinations thereof.

Carbon

In other embodiments, the coating composition can include inert carbon.Suitable forms of inert carbon can include with out limitation,pyrolitic carbon and porous vitreous carbon. Use of porous carbon canhelp prevent thrombosis and encourage endothelial cell growth.

The coating materials can comprise at least 5%, at least 10%, at least20%, at least 30%, at least 40%, at least 50%, at least 60%, at least70%, at least 80%, at least 90%, at least 95%, at least 97%, at least99% or more by weight of the coating composition. In certain embodimentswhere a coating composition includes a polymer, the polymer is about 60%to about 99% by weight of the coating composition. In certainembodiments, where a coating composition includes a metal oxide orceramic oxide, the metal oxide or ceramic oxide is about 0.1% to about5% by weight of the coating composition. In certain embodiments, where acoating composition includes a metal, the metal is about 0.1% to about20% by weight of the coating composition. In certain embodiments, wherea coating composition includes carbon, the carbon is about 0.1% to about50% by weight of the coating composition.

In certain embodiments, the coating composition that has an exposedabluminal surface is free of polymer or substantially free of a polymer.Used herein substantially free of polymer means that any polymerincluded in the first coating composition is less than 50% by weight ofthe first coating composition. In such embodiments, the coatingcompositions can include any of the metal oxides, ceramic oxides, metalsor carbons discussed above.

Intervening Materials

Additionally, certain embodiments of the coatings described hereininclude an intervening material. Suitable intervening materials enhancethe adhesion of the coating compositions to other coating compositionsor to the surface of the medical device. Intervening materials include,but are not limited to, adhesive materials or textured materials.Suitable adhesive materials include, but are not limited to, parylene C.Suitable textured materials are materials that have a texture thatimproves the adhesion of the coating composition and can compriseiridium oxides, zirconium oxides, platinum oxides, titanium oxides,tantalum oxides, zinc oxides, iron oxides, magnesium oxides, aluminumoxides, niobium oxides, tungsten oxides, rhodium oxides, rutheniumoxides, silicon oxides or a combination thereof. Textures can be formedby any methods known in the art including, but not limited to laserpitting, micro blasting, sputter coating a thin film, physical vapordeposition, chemical etching, and standard lithographic techniques, suchas micro contact printing and photolithography.

C. Therapeutic Agents

The term “therapeutic agent” as used herein encompasses drugs, geneticmaterials, and biological materials and can be used interchangeably with“biologically active material.” The term “genetic materials” means DNAor RNA, including, without limitation, DNA/RNA encoding a useful proteinstated below, intended to be inserted into a human body including viralvectors and non-viral vectors.

The term “biological materials” include cells, yeasts, bacteria,proteins, peptides, cytokines and hormones. Examples for peptides andproteins include vascular endothelial growth factor (VEGF), transforminggrowth factor (TGF), fibroblast growth factor (FGF), epidermal growthfactor (EGF), cartilage growth factor (CGF), nerve growth factor (NGF),keratinocyte growth factor (KGF), skeletal growth factor (SGF),osteoblast-derived growth factor (BDGF), hepatocyte growth factor (HGF),insulin-like growth factor (IGF), cytokine growth factors (CGF),platelet-derived growth factor (PDGF), hypoxia inducible factor-1(HIF-1), stem cell derived factor (SDF), stem cell factor (SCF),endothelial cell growth supplement (ECGS), granulocyte macrophage colonystimulating factor (GM-CSF), growth differentiation factor (GDF),integrin modulating factor (IMF), calmodulin (CaM), thymidine kinase(TK), tumor necrosis factor (TNF), growth hormone (GH), bone morphogenicprotein (BMP) (e.g., BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7(PO-I), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-14, BMP-15, BMP-16,etc.), matrix metalloproteinase (MMP), tissue inhibitor of matrixmetalloproteinase (TIMP), cytokines, interleukin (e.g., IL-1, IL-2,IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-15,etc.), lymphokines, interferon, integrin, collagen (all types), elastin,fibrillins, fibronectin, vitronectin, laminin, glycosaminoglycans,proteoglycans, transferrin, cytotactin, cell binding domains (e.g.,RGD), and tenascin. Currently preferred BMP's are BMP-2, BMP-3, BMP-4,BMP-5, BMP-6, BMP-7. These dimeric proteins can be provided ashomodimers, heterodimers, or combinations thereof, alone or togetherwith other molecules. Cells can be of human origin (autologous orallogeneic) or from an animal source (xenogeneic), geneticallyengineered, if desired, to deliver proteins of interest at thetransplant site. The delivery media can be formulated as needed tomaintain cell function and viability. Cells include progenitor cells(e.g., endothelial progenitor cells), stem cells (e.g., mesenchymal,hematopoietic, neuronal), stromal cells, parenchymal cells,undifferentiated cells, fibroblasts, macrophage, and satellite cells.

Other suitable therapeutic agents include:

-   -   anti-thrombogenic agents such as heparin, heparin derivatives,        urokinase, and PPack (dextrophenylalanine proline arginine        chloromethylketone);    -   anti-proliferative agents such as enoxaprin, angiopeptin, or        monoclonal antibodies capable of blocking smooth muscle cell        proliferation, hirudin, acetylsalicylic acid, tacrolimus,        everolimus, pimecrolimus, sirolimus, zotarolimus, amlodipine and        doxazosin;    -   anti-inflammatory agents such as glucocorticoids, betamethasone,        dexamethasone, prednisolone, corticosterone, budesonide,        estrogen, sulfasalazine, rosiglitazone, mycophenolic acid and        mesalamine;    -   anti-neoplastic/anti-proliferative/anti-miotic agents such as        paclitaxel, 5-fluorouracil, cisplatin, vinblastine, vincristine,        epothilones, methotrexate, azathioprine, adriamycin and        mutamycin; endostatin, angiostatin and thymidine kinase        inhibitors, cladribine, taxol and its analogs or derivatives,        paclitaxel as well as its derivatives, analogs or paclitaxel        bound to proteins, e.g. Abraxane™;    -   anesthetic agents such as lidocaine, bupivacaine, and        ropivacaine;    -   anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an        RGD peptide-containing compound, heparin, antithrombin        compounds, platelet receptor antagonists, anti-thrombin        antibodies, anti-platelet receptor antibodies, aspirin (aspirin        is also classified as an analgesic, antipyretic and        anti-inflammatory drug), dipyridamole, protamine, hirudin,        prostaglandin inhibitors, platelet inhibitors, antiplatelet        agents such as trapidil or liprostin and tick antiplatelet        peptides;    -   DNA demethylating drugs such as 5-azacytidine, which is also        categorized as a RNA or DNA metabolite that inhibit cell growth        and induce apoptosis in certain cancer cells;    -   vascular cell growth promoters such as growth factors, vascular        endothelial growth factors (VEGF, all types including VEGF-2),        growth factor receptors, transcriptional activators, and        translational promoters;    -   vascular cell growth inhibitors such as anti-proliferative        agents, growth factor inhibitors, growth factor receptor        antagonists, transcriptional repressors, translational        repressors, replication inhibitors, inhibitory antibodies,        antibodies directed against growth factors, bifunctional        molecules consisting of a growth factor and a cytotoxin,        bifunctional molecules consisting of an antibody and a        cytotoxin;    -   cholesterol-lowering agents, vasodilating agents, and agents        which interfere with endogenous vasoactive mechanisms;    -   anti-oxidants, such as probucol;    -   antibiotic agents, such as penicillin, cefoxitin, oxacillin,        tobranycin, daunomycin, mitocycin;    -   angiogenic substances, such as acidic and basic fibroblast        growth factors, estrogen including estradiol (E2), estriol (E3)        and 17-beta estradiol;    -   drugs for heart failure, such as digoxin, beta-blockers,        angiotensin-converting enzyme (ACE) inhibitors including        captopril and enalopril, statins and related compounds;    -   macrolides such as sirolimus (rapamycin) or everolimus; and    -   AGE-breakers including alagebrium chloride (ALT-711).

Other therapeutic agents include nitroglycerin, nitrous oxides, nitricoxides, antibiotics, aspirins, digitalis, estrogen, estradiol andglycosides. Preferred therapeutic agents include anti-proliferativedrugs such as steroids, vitamins, and restenosis-inhibiting agents.Preferred restenosis-inhibiting agents include microtubule stabilizingagents such as Taxol®, paclitaxel (i.e., paclitaxel, paclitaxel analogs,or paclitaxel derivatives, and mixtures thereof). For example,derivatives suitable for use in the embodiments described herein include2′-succinyl-taxol, 2′-succinyl-taxol triethanolamine, 2′-glutaryl-taxol,T-glutaryl-taxol triethanolamine salt, 2′-O-ester withN-(dimethylaminoethyl) glutamine, and 2′-O-ester withN-(dimethylaminoethyl) glutamide hydrochloride salt.

Other preferred therapeutic agents include tacrolimus; halofuginone;inhibitors of HSP90 heat shock proteins such as geldanamycin;microtubule stabilizing agents such as epothilone D; phosphodiesteraseinhibitors such as cliostazole; Barkct inhibitors; phospholambaninhibitors; and Serca 2 gene/proteins. In yet another preferredembodiment, the therapeutic agent is an antibiotic such as erythromycin,amphotericin, rapamycin, adriamycin, etc.

In preferred embodiments, the therapeutic agent comprises daunomycin,mitocycin, dexamethasone, everolimus, tacrolimus, zotarolimus, heparin,aspirin, warfarin, ticlopidine, salsalate, diflunisal, ibuprofen,ketoprofen, nabumetone, prioxicam, naproxen, diclofenac, indomethacin,sulindac, tolmetin, etodolac, ketorolac, oxaprozin, celcoxib, alagebriumchloride or a combination thereof.

The therapeutic agents can be synthesized by methods well known to oneskilled in the art. Alternatively, the therapeutic agents can bepurchased from chemical and pharmaceutical companies.

In some embodiments, the therapeutic agent comprises at least 1%, atleast 5%, at least 10%, at least 15%, at least 20%, at least 30%, atleast 40% or more by weight of the coating composition. Weights lessthan 15% generally allow the agent to elute into the body by diffusionthrough the polymer matrix. Weights between 15-20% result in fasterdiffusion, as the agent is allowed to diffuse through voids left bypreviously-eluted agent. Preferably, the therapeutic agent is between 1%and 30% by weight of the coating composition. In certain embodiments,the therapeutic agent is about 15% by weight of the coating composition.

D. Methods of Making Coatings

Also described herein are methods of making a coated medical device.Methods discussed herein include the steps of disposing a coatingcomposition on at least a portion of the surface of a medical devicesuch that the coating composition has an exposed abluminal surface andan exposed luminal surface or an exposed side surface.

In certain embodiments, the coated medical devices can be made bydisposing a coating composition on at least a portion of the surface ofa medical device and removing a portion of the coating composition, sothat the coating composition has an exposed abluminal surface and anexposed luminal surface.

FIG. 9A shows one embodiment of a method of making a coated medicaldevice. As shown in FIG. 9A, a coating composition 600 is disposeddirectly on a portion of a surface 610 of medical device 612. Then aportion of the coating composition is removed, as shown in FIG. 9B, sothat the coating composition 600 disposed on the surface 610 of amedical device 612 has an exposed abluminal surface 620, an exposedluminal surface 622 and exposed side surfaces 624.

The coatings described herein can also be made by disposing a secondarymaterial or masking material on at least a portion of the surface of amedical device, such as an intervascular stent. A coating composition isthen disposed on at least a portion of the surface of a medical deviceand on a portion of the secondary material or masking material. Thesecondary material or masking material is removed such that the coatingcomposition has an exposed abluminal surface, an exposed luminal surfaceand exposed side surfaces. Such a method is shown in FIGS. 10A through10C. FIG. 10A shows a secondary material or masking material 730disposed on a portion of the surface 710 of the medical device 712. Acoating composition 700 is then disposed on the medical device 712, asshown in FIG. 10B. Once the coating composition 700 is disposed on themedical device 712, the secondary material or masking material 730 canbe removed, such that the coating composition 700 has an exposedabluminal surface 720, an exposed luminal surface 722 and exposed sidesurfaces 724, as shown in FIG. 10C. In certain methods, the secondarymaterial can be mixed with the coating composition wherein the coatingcomposition and the secondary material can be disposed on the surface ofthe medical device simultaneously.

The above methods can further include the steps of disposing anintervening material on at least a portion of the surface of the medicaldevice. The intervening material can be disposed on the surface of themedical device after the secondary material or masking material has beendisposed on at least a portion of the surface of the medical device. Thecoating composition can then be disposed on at least a portion of theintervening material and the secondary material or masking material.Then the secondary material or masking material can be removed.

The methods of coating a medical device, preferably, an implantablestent, described herein include the steps of disposing a first coatingcomposition on at least a portion of the abluminal surface; anddisposing a second coating composition on the first coating compositionsuch that the second coating composition has an exposed abluminalsurface and an exposed luminal surface or exposed side surfaces.

In certain embodiments, the methods of coating an implantable stentdescribed herein include the steps of disposing a first coatingcomposition on at least a portion of the abluminal surface; removing atleast a portion of the first coating composition; disposing a secondcoating composition on the first coating composition; and removing atleast a portion of the second coating composition such that the secondcoating composition has an exposed abluminal surface and an exposedluminal surface, as shown in FIGS. 11A through 11D.

As shown in FIG. 11A, a first coating composition 800 is disposed on aportion of a surface 810 of medical device 812. A portion of the firstcoating composition 800 is then removed as shown in FIG. 11B. Once atleast a portion of the first coating composition 800 has been removedfrom at least a portion of the surface 810 of the medical device 812, asecond coating composition 820 is disposed on the first coatingcomposition 800 as shown in FIG. 11C. Once the second coatingcomposition 820 is disposed on the first coating composition 800, ifnecessary, a portion of the second coating composition 820 is removed sothat the second coating composition 820 has an exposed abluminal surface822, an exposed luminal surface 824 and exposed side surfaces 826, asshown in FIG. 11D.

Another embodiment of the methods described herein is shown in FIGS.12A-12D, which includes the steps of disposing a secondary material ormasking material 900 on a portion of the abluminal surface 910 of amedical device 920, as shown in FIG. 12A. This embodiment is similar tothe described in connection with FIGS. 10A-10C. However, this embodimentinvolves two coating compositions. A first coating composition 930 canbe disposed on at least a portion of the abluminal surface 910 of themedical device 920, as shown in FIG. 12B, between the secondary material900. A second coating composition 940 can then be disposed on at least aportion of the first coating composition 930 and at least a portion ofthe secondary material or masking material 900, as shown in FIG. 12C.The secondary material or masking material 900 can be removed such thatthe second coating composition 940 has an exposed abluminal surface 950,an exposed luminal surface 960 and exposed side surfaces 970, as shownin FIG. 12D.

The above methods can further include the step of disposing anintervening material on the first coating composition prior to disposingthe second coating composition on the first coating composition.Alternatively, the above methods can further include the step ofdisposing an intervening material on the surface of the medical deviceprior to disposing the first coating composition on the medical device,such that the intervening material is between the surface of the medicaldevice and the first coating composition.

The methods of coating a medical device, preferably, an implantablestent, described herein also include the steps of disposing a firstcoating composition on at least a portion of the abluminal surface;disposing a second coating composition on the first coating composition;and disposing a third coating composition on the second coatingcomposition such that the third coating composition has an exposedabluminal surface and an exposed luminal surface or an exposed sidesurface. FIGS. 13A-13E show such an embodiment. This method includes thestep of disposing a first coating composition 1000 on at least a portionof the abluminal surface 1010 of a stent strut 1020, as shown in FIG.13A. At least a portion of the first coating composition 1000 can beremoved, as shown in FIG. 13B. A second coating composition 1030 canthen be disposed on the first coating composition 1000, as shown in FIG.13C. At least a portion of the second coating composition 1030 can beremoved, as shown in FIG. 13D and then a third coating composition 1040can be disposed on the second coating composition 1030 such that thethird coating composition 1040 has an exposed abluminal surface 1050, anexposed luminal surface 1060 and exposed side surfaces 1070, as shown inFIG. 13E. Embodiments of coatings made from such methods are shown inFIG. 4A.

In certain embodiments, methods of coating an implantable stent as shownin FIGS. 14A-14C, include the steps of disposing a first coatingcomposition on at least a portion of the abluminal surface of a stentstrut and disposing a second coating composition on the first coatingcomposition, wherein once disposed on at least a portion of the firstcoating composition, the second coating composition has an exposedabluminal surface and an exposed luminal surface or exposed side surfaceand wherein the second coating composition is prefabricated to conformto the stent. Preferably, the prefabricated second coating compositionis prefabricated to conform to the stent. FIG. 14A shows a first coatingcomposition 1100 disposed on at least a portion of the abluminal surface1110 of a stent strut 1120. FIG. 14B shows a second coating composition1130 that is prefabricated. FIG. 14C shows the prefabricated secondcoating composition 1130 disposed on the first coating composition 1100,wherein once disposed on at least a portion of the first coatingcomposition 1100, the second coating composition 1130 has an exposedabluminal surface 1140, an exposed luminal surface 1150 and exposed sidesurfaces 1160.

Coating compositions can be disposed on the medical device by any of thetechniques known in the art. Suitable method include, but are notlimited to, dipping, spraying, painting, electroplating, evaporation,plasma-vapor deposition, cathodic-arc deposition, sputtering, ionimplantation, electrostatically, electroplating, electrochemically, rollcoating, selective droplet deposition, ionic droplet deposition,drop-on-demand processes or a combination of any of the above.

Removal of at least a portion of the coating composition so that thecoating composition has an exposed abluminal surface and an exposedluminal surface or an exposed side surface can be done by any methodknown in the art. These methods include, but are not limited to, laserablation, drilling, or chemical etching.

The secondary material or masking material can be any material so longas it can be removed such that the coating composition has an exposedabluminal surface and an exposed luminal surface. For example, thesecondary material or masking material can be more electrochemicallyactive than the coating composition, or the secondary material ormasking material can be more soluble than the coating composition.Suitable secondary materials or masking materials include metals orpolymers.

Techniques for removing secondary materials or masking materialsinclude, but are not limited to, dissolution, dealloying or anodizationprocesses. The secondary material or masking material can be removedfrom the coating composition by a dealloying process. In this method,the first coating composition and the secondary material or maskingmaterial are exposed to an acid which removes the secondary material ormasking material. Thus, the coating composition is preferably one thatwill not dissolve when exposed to the acid, while the secondary metal ormasking material is one that will dissolve.

Alternatively, the secondary material or masking material can be removedanodically. For example, silver may be removed anodically using a dilutenitric acid bath comprising up to 15% nitric acid, wherein the anode isthe plated stent, and the cathode is platinum. Voltages up to 10V DC canbe applied across the electrodes. The bath chemistry, temperature,applied voltage, and process time may be varied to vary the geometry,distribution, and depth of the coating layer. In another example, aTechnic Envirostrip Ag 10-20 amps per square foot may be used with astainless steel cathode.

In any of the above embodiments, the coating compositions can include aplurality of pores. Pores can be formed by any means known to oneskilled in the art. Suitable methods of forming pores includemicro-roughing techniques involving the use of reactive plasmas or ionbombardment electrolyte etching, sand blasting, laser etching andchemical etching. Pores can be disposed in a pattern such as near theexposed surfaces of the coatings or pores can be formed throughout thecoatings described herein. Additionally, pores may occur naturally inthe coating material, depending on the coating material used. Forexample, some types of carbon and polymers, suitable as coatingcompositions contain pores.

Additionally, in any of the above embodiments, any of the coatingcompositions can include at least one therapeutic agent. In certainembodiments, the therapeutic agent is disposed within the pores. Tofacilitate disposing a therapeutic agent in the pores, a solution orsuspension of a the therapeutic agent can be formed by dissolving orsuspending the therapeutic agent in an organic or aqueous solvent whichis then used to dispose the therapeutic agent in the pores.

The medical devices and stents described herein may be used for anyappropriate medical procedure. Delivery of the medical device can beaccomplished using methods well known to those skilled in the art.

The description provided herein is not to be limited in scope by thespecific embodiments described which are intended as singleillustrations of individual aspects of certain embodiments. The methods,compositions and devices described herein can comprise any featuredescribed herein either alone or in combination with any otherfeature(s) described herein. Indeed, various modifications, in additionto those shown and described herein, will become apparent to thoseskilled in the art from the foregoing description and accompanyingdrawings using no more than routine experimentation. Such modificationsand equivalents are intended to fall within the scope of the appendedclaims.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated by reference in their entiretyinto the specification to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Citationor discussion of a reference herein shall not be construed as anadmission that such is prior art.

What is claimed is:
 1. An implantable stent comprising: (a) a stentsidewall structure having an abluminal surface and a luminal surfaceopposite the abluminal surface, the luminal surface being an outersurface of the stent sidewall structure and the abluminal surface beingan inner surface of the stent sidewall structure, when the stentsidewall structure is delivered in a body lumen, the luminal surface tobe at least partially exposed to face a lumen wall of the body lumen,and the adluminal surface to be at least partially exposed to face awayfrom the lumen wall; and wherein the coating has a cross-section in theshape of a “T”, (b) a coating comprising a coating composition disposedover at least a portion of the abluminal surface of the stent sidewallstructure, wherein the coating has an exposed abluminal surface to faceaway from the abluminal surface of the stent sidewall structure and anexposed luminal surface to face the abluminal surface of the stentsidewall structure, and wherein the coating composition comprises atherapeutic agent.
 2. The stent of claim 1, wherein the coatingcomposition is disposed directly on the abluminal surface of the stent.3. The stent of claim 1, wherein the coating further comprises anadhesive material disposed between the abluminal surface of the stentand the coating composition.
 4. The stent of claim 1, wherein thetherapeutic agent comprises an anti-thrombogenic agent,anti-angiogenesis agent, anti-proliferative agent, antibiotic,anti-restenosis agent, growth factor, immunosuppressant, or aradiochemical.
 5. The stent of claim 1, wherein the therapeutic agentcomprises paclitaxel, sirolimus, tacrolimus, pimecrolimus, everolimus,or zotarolimus.
 6. The stent of claim 1, wherein the coating compositioncomprises a polymer, metal, metal oxide, ceramic oxide, inert carbon orcombination thereof.
 7. The stent of claim 1, wherein the coatingcomposition comprises a biostable polymer and the therapeutic agentcomprises an anti-restenosis agent.
 8. The stent of claim 1, wherein thecoating further comprises a first coating composition disposed over atleast a portion of the abluminal surface, and wherein the coatingcomposition is a second coating composition disposed on the firstcoating composition.
 9. The stent of claim 8, wherein the first coatingcomposition is disposed directly on the abluminal surface and the secondcoating composition is disposed directly on the first coatingcomposition.
 10. The stent of claim 8, wherein the coating furthercomprises an adhesive material disposed between the abluminal surface ofthe stent and the first coating composition.
 11. The stent of claim 10,wherein the stent further comprises an adhesive material disposedbetween the first coating composition and the second coatingcomposition.
 12. The stent of claim 8, wherein the first and secondcoating compositions are different.
 13. The stent of claim 8, whereinthe first coating composition and the second coating composition are thesame.
 14. The stent of claim 8, wherein the first coating compositioncomprises a first exposed surface area when disposed on the abluminalsurface and the second coating composition comprises a second exposedsurface area when disposed on the first coating composition, wherein thesecond exposed surface area is greater than the first exposed surfacearea.
 15. The stent of claim 8, wherein the first coating composition orthe second coating composition comprises a therapeutic agent.
 16. Thestent of claim 15, wherein the therapeutic agent comprises ananti-thrombogenic agent, anti-angiogenesis agent, anti-proliferativeagent, antibiotic, anti-restenosis agent, growth factor,immunosuppressant, or a radiochemical.
 17. The stent of claim 15,wherein the therapeutic agent comprises paclitaxel, sirolimus,tacrolimus, pimecrolimus, everolimus, or zotarolimus.
 18. The stent ofclaim 8, wherein the first coating composition or the second coatingcomposition comprise a polymer, metal, metal oxide, ceramic oxide, inertcarbon or combination thereof.
 19. The stent of claim 8, wherein thefirst coating composition comprises a first biostable polymer and isdisposed directly on the at least a portion of the abluminal surface ofthe strut; and wherein the second coating composition is disposeddirectly on the first coating composition and comprises a secondbiostable polymer and an anti-restenosis agent.
 20. The stent of claim8, wherein the coating further comprises: a third coating compositiondisposed over the second coating composition, the third coatingcomposition having the exposed abluminal surface and the exposed luminalsurface.
 21. The stent of claim 20, wherein the coating furthercomprises an adhesive material disposed between the abluminal surface ofthe stent and the first coating composition.
 22. The stent of claim 20,wherein the coating further comprises an adhesive material disposedbetween the first coating composition and the second coatingcomposition.
 23. The stent of claim 20, wherein at least one of thecoating compositions is different from the other two.
 24. The stent ofclaim 20, wherein the first coating composition, the second coatingcomposition or the third coating composition comprise a therapeuticagent.
 25. The stent of claim 24, wherein the therapeutic agentcomprises an anti-thrombogenic agent, anti-angiogenesis agent,antiproliferative agent, antibiotic, anti-restenosis agent, growthfactor, immunosuppressant, or a radiochemical.
 26. The stent of claim24, wherein the therapeutic agent comprises paclitaxel, sirolimus,tacrolimus, pimecrolimus, everolimus, or zotarolimus.
 27. The stent ofclaim 1, wherein the shape of a “T” comprises a “T” with rounded edgesand curved surfaces.
 28. The stent of claim 1, wherein the shape of a“T” comprises a “T” with ridges.
 29. The stent of claim 8, wherein thesecond coating composition has the exposed abluminal surface and theexposed luminal surface.